Neonatal CD8+ T-cell differentiation is dependent on interleukin-12

Neonatal CD8(+) T-cell activation is significantly impaired compared with that in adults Recent studies have demonstrated that interleukin (IL)-12 is necessary as a third signal in addition to antigen and co-stimulation to authorize the differentiation of naive CD8(+) T cells We examined whether human neonatal CD8(+) T cells which possess an exclusively naive T-cell phenotype required a third signal to authorize a productive T-cell response IL-12 enhanced activated naive CD8(+) T-cell survival expansion CD25 expression and IL-2 production Activated CD8(+) T cells produced interferon-gamma and intracellular granzyme B and were cytotoxic only in the presence of IL 12 Sustained IL-12 signaling for 72 hours was required for optimal interferon-gamma production IL-12 in concert with T cell receptor (TCR) stimulation sustained late stage (48 -72 hours) intracellular phosphorylanon and particularly total protein levels of the proximal TCR components Lck and CD3 xi The requirement for a third signal for productive human neonatal CD8(+) T-cell differentiation may have implications for neonatal vaccination strategies (C) 2010 American Society for Histocompatibility and Immunogenetics Published by Elsevier Inc All rights reserved